Insulin, the negative control of beta2 adrenergic receptor

Insulin is the most potent antilipolytic hormone. Lipolysis is a crucial step in metabolism where a fat storage (TG) changed into ready to use fat (FA). Because this process affect the whole human energy metabolism, it should be controlled throughoughly. Cathecolamine, a signal from the brain, is the major regulator of lipolysis since its ability to induce beta2AR stimulation of lipolysis. However, our body seems has another way to control or stop this process. One of the mechanism, out of negative feedbak mechanism, is by using insulin.

The importance of insulin for controling lipolysis is that to make sure that body use glucose instead of fatty acid where the amount of glucose increased. Thus, metabolism shifted from using fatty acid as the source of energy into using glucose. In the simple words this signal says “hey, stop breaking fat. We have enough glocose to burn”. After insulin signal given to the adipose tissue, fatty acid will stay in the depot and those will be subjects for reesterification. This idea then supported by studies showing that lipolysis process could be stopped by using insulin. Hormon sensitive lipase (HSL) action decrease after infusion of insulin. There factors also regulate lipolysis, those including adenosine, ketone bodies and blood flow.

Some interesting progress were made after they found that insulin play role in fat metabolism through lipolysis inhibition. In model of obesity, where body has abundance of energy stored as fat, hyperinsulinemia and insulin resistance also exist. This properties also found in human obese based at population study. A study done in rat shown that obesity is related to decrease both betaAR expression and function. This was also seen by the fact that animal model develop obesity also has a problem with high level on insulin. The other study in rat model supported this finding by showing that reducing hyperinsulinemia would help increase lipolysis and reduce adipose tissue mass.

Insulin action on fat metabolism in adipose tissue was done via PKB pathway. The stimulation of insulin receptor would lead to counteract with cAMP production throusgh cyclic nucleotide phosphodiesterase 3B. This process will then stop downstream pathway of betaAR. This phenomena is not much studied. However, if hyperinsulinemia is really linked to insensitivity of betaAR, this could explain why people with obesity are more likely develop insensitiviy of beta2AR.